Date of Award

Summer 8-13-2014

Degree Type

Dissertation

Degree Name

Ph.D.

Degree Program

Chemistry

Department

Chemistry

Major Professor

Matthew A. Tarr

Second Advisor

Mark Trudell

Third Advisor

John Wiley

Fourth Advisor

Yang Cai

Abstract

Progress has been made in using human serum albumin nanoparticles (HSAPs) as carrier systems for targeted treatment of cancer. Human serum albumin (HSA), the most abundant human blood protein, can form HSAPs via a desolvation and crosslinking method, with the size of the HSAPs having crucial importance for drug loading and in vivo performance. Gold nanoparticles have also gained medicinal attention due to their ability to absorb near-infrared (NIR) light. These relatively non-toxic particles offer combinational therapy via imaging and photothermal therapy (PPTT) capabilities.

A desolvation and crosslinking approach was employed to encapsulate gold nanoparticles (AuNPs), hollow gold nanoshells (AuNSs), and gold nanorods (AuNRs), into efficiently sized HSAPs for future tumor heat ablation via PPTT. The AuNR-HSAPs, AuNP-HSAPs and AuNS-HSAPs had average particle diameters of 222 ± 5, 195 ± 9 and 156 ± 15, respectively.

We simultaneously encapsulated AuNRs and the anticancer drug paclitaxel (PAC), forming PAC-AuNR-HSAPs with overall average particle size of 299 ± 6 nm. Loading of paclitaxel into PAC-AuNR-HSAPs reached 3μg PAC/mg HSA. PAC-AuNR-HSAPs experienced photothermal heating of 46 ˚C after 15 minutes of NIR laser exposure; the temperature necessary to cause severe cellular hyperthermia. There was a burst release of paclitaxel up to 188 ng caused by the irradiation session, followed by a temporal drug release.

AuNR-HSAPs were tested for ablation of renal cell carcinoma using NIR irradiation in vitro. Particles created with the same amount of AuNRs, but varying HSA (1, 5 or 20 mg) showed overall particle size diameters 409 ± 224, 294 ± 83 and 167 ± 4 nm, respectively. Increasing HSAPs causes more toxicity under non-irradiated treatment conditions: AuNR-HSAPs with 20 mg versus 5 mg HSA caused cell viability of 64.5% versus 87%, respectively. All AuNR-HSAPs batches experienced photothermal heating above 42 ˚C. Coumarin-6, was used to visualize the cellular uptake of AuNR-HSAPs via fluorescence microscopy.

Finally, camptothecin (CPT) an antineoplastic agent and BACPT (7-butyl-10-aminocamptothecin) were loaded into HSAPs to combat their aqueous insolubility. BACPT-HSAPs loaded up to 5.25 micrograms BACPT/ mg of HSA. CPT encapsulation could not be determined. BACPT-HSAPs and CPT-HSAPs showed cytotoxicity to human sarcoma cells in vitro.

Rights

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